Is CREB the Angry Bird that Releases Memory in Alzheimer's?

Wang, Allan; Bibb, James A.

doi:10.1038/npp.2011.126

Cited by 11 publications

(12 citation statements)

References 8 publications

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“…Calpain regulates the activity of a number of proteins that are part of processes influencing neuronal plasticity, cognition and neurodegeneration 25 . CREB is a key protein in synaptic plasticity, impaired activation of which is a key contributor to pathogenesis of Alzheimer׳s disease (AD) 26 , 27 , 28 , 29 . CREB is a substrate of calpain, and thus inhibitors have been demonstrated to increase CREB phosphorylation, in turn restoring synaptic plasticity in the APP/PS1 transgenic mouse model of familial AD 30 .…”

Section: Cysteine Proteasesmentioning

confidence: 99%

Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors

Siklos

BenAissa

Thatcher

2015

Acta Pharmaceutica Sinica B

200

169

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Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.

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Section: Cysteine Proteasesmentioning

confidence: 99%

Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors

Siklos

BenAissa

Thatcher

2015

Acta Pharmaceutica Sinica B

200

169

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“…An increase in CAMII, CREB, p38 signalling could be required for mediating morphine tolerance. 48 Thus, together the results suggest that the microglial induced neuronal CXCR3 activation could develop morphine tolerance possibly via CaMKII/CREB/p38 signalling.…”

Section: Resultsmentioning

confidence: 78%

“…Overall findings indicate that, in the spinal cord, CXCL10 negatively regulates morphine analgesia suggesting that the CXCL10/CXCR3 activation can reduce the analgesic effects of morphine in relieving BCP. 48 It is possible that the interactions between CXCR3 and MOR in the brain stem could be a critical step in causing morphine-induced hyperalgesia, central sensitisation and opioid tolerance. In these studies, CXCL10 appears to be a strong pain-producing agent, whereas the CXCR3 blockade using an antagonist could be an effective analgesic option and it would be interesting to measure its effects on morphine tolerance.…”

Section: Resultsmentioning

confidence: 99%

<p>Evaluating the Role of CXCR3 in Pain Modulation: A Literature Review</p>

Aloyouny

Bepari

Rahman

2020

JPR

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CXCR3 is a well-known receptor involved in immune cell recruitment and inflammation. Pathological inflammation leads to pain stimulation and hence nociception. Therefore, we decided to review the recent research on CXCR3 to identify its precise role in the modulation of pain in a variety of clinical conditions targeting various regions of the body. Studies were selected from PubMed Medline, which relate CXCR3 to the progression of diseases with either bone cancer pain, neuropathic pain, cystitis pain, osteoarthritis and rheumatoid arthritis pain, dental pain, in particular, periodontitis and pulpitis. In all the diseases studied, a high prevalence of CXCR3 and/or its ligand were identified where CXCR3 is a key player in the pathophysiological process of many inflammatory conditions. CXCR3 and its ligands, particularly CXCL10, modulate nociception via actions in the dorsal root ganglia and dorsal horn of the spinal cord, in cases of bone cancer pain, neuropathic, and joint pain. However, with the other studied disease, no direct link to pain has been made, although it contributes to the pathological progression of the diseases and hence would be a causal factor for the pain. Furthermore, CXCR3 appears to play a role in desensitizing the opioid receptor in the descending modulatory pathway within the brain stem as well as modulating opioid-induced hyperalgesia in the dorsal horn of the spinal cord. Further research is required for understanding the exact mechanisms of CXCR3 in pain modulation centrally and peripherally. A greater understanding of the immunological activities and pharmacological consequence of CXCR3 and its ligands could help in the discovery of newer drugs for modulating pain arising from pathogenic or inflammatory sources. Given the significance of the CXCR3 for nociception, its utilization may prove to be beneficial as a target for analgesia.

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“…Of particular interest is the transcription factor CREB1 (aka CREB), the cAMP-response element binding protein, along with two G-protein coupled receptors (GPR1 and GPR155) which may be involved in the CREB signaling pathway, due to the associations of CREB with AD [27][28][29][30][31] . Mutations in the presenilin genes lead to early-onset familial AD, and it has been demonstrated in vitro and in vivo that expression of these mutant genes leads to constitutive CREB phosphorylation 28 .…”

Section: Discussionmentioning

confidence: 99%

Synchronized genetic activities in Alzheimer’s brains revealed by heterogeneity-capturing network analysis

Climer

Templeton

Garvin

et al. 2020

Preprint

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It is becoming increasingly evident that the efficacy of single-gene computational analyses for complex traits is nearly exhausted and future advances hinge on unraveling the intricate combinatorial interactions among multiple genes. However, the discovery of modules of genes working in concert to manifest a complex trait has been crippled by combinatorial complexity, genetic heterogeneity, and validation biases. We introduce Maestro, a novel network approach that employs a multifaceted correlation measure, which captures heterogeneity, and a rigorous validation method. Maestro's utilization for Alzheimer's disease (AD) reveals an expression pattern that has virtually zero probability of simultaneous expression by an individual, assuming independence. Yet this pattern is exhibited by 19.0% of AD cases and 7.3% of controls, establishing an unprecedented pattern of synchronized genetic activities in the human brain. This pattern is significantly associated with AD, with an odds ratio of 3.0. This study substantiates Maestro's power for discovery of orchestrated genetic activities underlying complex traits. More generally, Maestro can be applied in diverse domains in which heterogeneity exists.

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Is CREB the Angry Bird that Releases Memory in Alzheimer's?

Cited by 11 publications

References 8 publications

Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors

Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors

<p>Evaluating the Role of CXCR3 in Pain Modulation: A Literature Review</p>

Synchronized genetic activities in Alzheimer’s brains revealed by heterogeneity-capturing network analysis

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